ANTIBODIES THAT IMMUNOSPECIFICALLY BIND TO B LYMPHOCYTE STIMULATOR PROTEIN

• US 20110117093A1
• Filed: 10/28/2010
• Published: 05/19/2011
• Est. Priority Date: 06/16/2000
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: RUBEN, Steven M., HILBERT, David, CHOI, Gil H., VAUGHAN, Tristan, BARASH, Steven C.
• Application Number:
  US12/914,741
• Publication Number:
  US 20110117093A1
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5011 : for testing antineoplastic activity
• CPC Class Codes: G01N 33/5052 : involving B-cells
• CPC Class Codes: G01N 33/5091 : for testing the pathological state of an organism
• CPC Class Codes: G01N 33/564 : for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/574 : for cancer
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

Claims

1. A method of treating an individual clinically diagnosed with an autoimmune disease, comprising:

analyzing a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA protein expression levels on their B cells, wherein the presence of elevated BCMA protein expression levels is associated with the clinical diagnosis of autoimmune disease; and

selecting a treatment plan that is most effective for individuals clinically diagnosed as having a condition associated with an increased BCMA protein expression level.

2. The method of claim 1 wherein said treatment plan involves administration of a BLyS antagonist.

3. The method of claim 2 wherein said BLyS antagonist is also an APRIL antagonist.

4. The method of claim 1, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener'"'"'s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

5. The method of claim 1 wherein said autoimmune disease is SLE.

6. A method for predicting a patient'"'"'s likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA protein expression on the patient'"'"'s B cells, wherein the presence of elevated BCMA protein expression levels is predictive of the patient'"'"'s likelihood to respond to a drug treatment for the condition.

7. The method of claim 6 wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener'"'"'s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

8. The method of claim 6 wherein said autoimmune disease is SLE.

9. The method of claim 6 wherein said drug treatment involves administration of a BLyS antagonist.

10. The method of claim 9 wherein said BLyS antagonist is also an APRIL antagonist.

11. An in vitro method of selecting a treatment plan that is most effective for treating an individual clinically diagnosed with an autoimmune disease, comprising:

analyzing in vitro a biological sample from an individual clinically diagnosed with autoimmune disease for the presence or absence of elevated BCMA levels on their B cells, wherein the presence of elevated BCMA levels is associated with the clinical diagnosis of autoimmune disease.

12. The method of claim 11 wherein said treatment plan involves the use of a BLyS antagonist.

13. The method of claim 12 wherein said BLyS antagonist is also an APRIL antagonist.

14. The method of claim 11, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener'"'"'s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

15. The method of claim 11 wherein said autoimmune disease is SLE.

16. An in vitro method for predicting a patient'"'"'s likelihood to respond to a drug treatment for an autoimmune disease, comprising determining the level of BCMA expression on the surface of B cells in a sample from the patient;

wherein the presence of elevated B cell levels is predictive of the patient'"'"'s likelihood to respond to a drug treatment for the condition.

17. The method of claim 16 wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), lupus nephritis (LN), Wegener'"'"'s disease, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

18. The method of claim 16 wherein said autoimmune disease is SLE.

19. The method of claim 16 wherein said drug treatment comprises a BLyS antagonist.

20. The method of claim 19 wherein said BLyS antagonist is also an APRIL antagonist.

21. A BLyS antagonist for use in the treatment of an autoimmune disease in a patient, wherein said patient has elevated levels of BCMA expression on the surface of B cells.

22. The antagonist of claim 21 wherein the autoimmune disease is SLE.

23. The antagonist of claim 21 wherein said antagonist is a BLyS antibody.

24. The antagonist of claim 23 wherein said BLyS antibody is Lymphostat-B.

25. The antagonist of claim 23 wherein said antagonist is a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig.

26. The antagonist of claim 25 wherein said receptor-extracellular domain/Fc domain fusion protein is TACI-Ig.

27. The antagonist of claim 26 wherein said TACI-Ig is atacicept.

28. A method of treating an individual diagnosed with an autoimmune disease, comprising:

analyzing a biological sample from an individual diagnosed with an autoimmune disease for the presence or absence of elevated B Lymphocyte Stimulator receptor protein expression levels, wherein the presence of elevated B Lymphocyte Stimulator receptor protein expression levels is associated with the diagnosis of autoimmune disease; and

treating the individual.

29. The method of claim 28, wherein the method further comprises selecting a treatment plan that is most effective for individuals diagnosed as having a condition associated with an increased B Lymphocyte Stimulator receptor protein expression level prior to treating the individual

30. The method of claim 28, wherein the B Lymphocyte Stimulator receptor is BCMA.

31. The method of claim 29, wherein the B Lymphocyte Stimulator receptor is BCMA.

32. The method of claim 28, wherein treating the individual comprises administering a BLyS antagonist.

33. The method of claim 29, wherein the treatment plan involves administration of a BLyS antagonist.

34. The method of claim 28, wherein the BLyS antagonist is also an APRIL antagonist.

35. The method of claim 29, wherein the BLyS antagonist is also an APRIL antagonist.

36. The method of claim 28, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

37. The method of claim 29, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune throbocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

38. The method of claim 28, wherein the autoimmune disease is SLE.

39. The method of claim 29, wherein the autoimmune disease is SLE.

40. A method for determining whether or not a patient diagnosed with an autoimmune disease will respond to treatment with a BLyS antagonist, comprising determining the level of B Lymphocyte Stimulator receptor protein expression on the patient'"'"'s cells, wherein the presence of elevated B Lymphocyte Stimulator receptor protein expression levels is indicative of whether or not the patient will respond to the treatment.

41. The method of claim 40, wherein the B Lymphocyte Stimulator receptor is BCMA.

42. The method of claim 40, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

43. The method of claim 40, wherein the autoimmune disease is SLE.

44. The method of claim 40, wherein the BLyS antagonist is also an APRIL antagonist.

45. An in vitro method of selecting a treatment that is most effective for treating an individual diagnosed with an autoimmune disease, comprising analyzing in vitro a biological sample from an individual diagnosed with an autoimmune disease for the presence or absence of elevated B Lymphocyte Stimulator receptor levels on their cells, wherein the presence of elevated B Lymphocyte Stimulator receptor levels is associated with the diagnosis of the autoimmune disease.

46. The method of claim 45, wherein the B Lymphocyte Stimulator receptor is BCMA.

47. The method of claim 45, wherein the treatment involves the use of a BLyS antagonist.

48. The method of claim 47, wherein the BLyS antagonist is also an APRIL antagonist.

49. The method of claim 45, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

50. The method of claim 45, wherein the autoimmune disease is SLE.

51. An in vitro method for determining whether or not a patient diagnosed with an autoimmune disease will respond to treatment with a BLyS antagonist, comprising determining the level of B Lymphocyte Stimulator receptor expression on the surface of cells in a sample from the patient;

wherein the presence of elevated B Lymphocyte Stimulator receptor levels is indicative of whether or not the patient will respond to the treatment.

52. The method of claim 51, wherein the B Lymphocyte Stimulator receptor is BCMA.

53. The method of claim 51, wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus (SLE), nephritis associated with systemic lupus erythematosus, inflammatory bowel disease, idiopathic thrombocytopenic purpura (ITP), autoimmune thrombocytopenic purpura, autoimmune thrombocytopenia, multiple sclerosis, psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, vasculitis, diabetes mellitus, Reynaud'"'"'s syndrome, Sjorgen'"'"'s syndrome and glomerulonephritis.

54. The method of claim 51, wherein the autoimmune disease is SLE.

55. The method of claim 51, wherein the BLyS antagonist is also an APRIL antagonist.

56. A BLyS antagonist for use in the treatment of an autoimmune disease in a patient, wherein the patient has elevated levels of B Lymphocyte Stimulator receptor expression on the surface of cells.

57. The antagonist of claim 56, wherein the B Lymphocyte Stimulator receptor is BCMA.

58. The antagonist of claim 56, wherein the autoimmune disease is SLE.

59. The antagonist of claim 56, wherein the antagonist is a BLyS antibody.

60. The antagonist of claim 59, wherein the BLyS antibody comprises amino acid residues 1-123 of SEQ ID NO:

327 and amino acid residues 141-249 of SEQ ID NO;

327.

61. The antagonist of claim 56, wherein the antagonist is a receptor-extracellular domain/Fc domain fusion protein selected from the group consisting of TACI-Ig, BCMA-Ig, and BAFF-R-Ig.

62. The antagonist of claim 56, wherein the receptor-extracellular domain/Fc domain fusion protein is TACI-Ig.